4.8 Article

Cellular T-cell immune response profiling by tetravalent dengue subunit vaccine (DSV4) candidate in mice

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FRONTIERS IN IMMUNOLOGY
卷 14, 期 -, 页码 -

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FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2023.1128784

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dengue vaccine; DSV4; BALB/c; type-specific immunity; ADE; T-cell; TNF-alpha; IFN-gamma

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Vaccines should stimulate both B-cell mediated humoral immunity and T-cell mediated cellular immunity. The pre-clinical tetravalent dengue subunit vaccine candidate, DSV4, can induce type-specific neutralizing antibody responses and dengue-specific T-cell responses in mice. These findings demonstrate that DSV4 can mediate both arms of adaptive immunity in mice.
While most vaccines aim to develop a solid humoral and neutralizing antibody response against the pathogen, an effective vaccine candidate should be able to stimulate both the B-cell mediated humoral immunity, and T-cell mediated cellular immunity. The focus of vaccinology is rapidly gaining to generate T cell responses, which can mediate pathogen clearance and help B cells leading to protective antibody responses. Here we evaluate the cellular immune response of the pre-clinical tetravalent dengue subunit vaccine candidate, DSV4, in mice. While we have shown previously that DSV4 induces type-specific neutralizing antibody responses in mice, in this study, we show that the vaccine candidate DSV4 well induces dengue-specific T- cell responses evaluated by their ability to produce IFN-gamma. In addition to IFN-gamma secretion by both CD4+ and CD8+ T-cells in immunized mice, we observed that DSV4 also induces a higher frequency and cytokine functions of follicular CD4+ helper T-cells (T-FH). These cytokines lead to an efficient germinal center reaction and potent B cell antibody response. Apart from TFH response, DSV4 stimulated Type 1 T helper cells (T-H1) which is characteristic of a viral infection leading to secretion of pro-inflammatory cytokines and phagocyte-dependent protective immune responses. Our study highlights that DSV4 can mediate both arms of adaptive immunity-humoral and cell-mediated immunity in mice. By elucidating vaccine-specific T cell response, our work has implications in showing DSV4 as an effective, type-specific and safe dengue vaccine candidate.

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